Factors Involved in the Development of Hypertension Induced by a Low-Protein Diet in Rats with Renal Injury

Abstract

Background/Aims: While a low-protein diet (LPD) has been reported to increase blood pressure, the mechanism for its increase has not yet been clarified. We investigated the factors involved in the development of hypertension induced by LPD in rats with post-cyclosporine (CsA) nephropathy, and determined the appropriate composition for LPD that is to be utilized for renal research. Methods: The rats were divided into 4 groups, each group being fed either a normal-protein diet (NPD), LPD with a low sucrose content as the main component of carbohydrate, LPD with a high-sucrose content, or LPD with low sucrose plus 2% L-arginine (Arg) for 12 weeks, and the blood pressure, urinary nitric oxide (NO) metabolite (NOx) excretion, renal NO-generating capacity and renal Arg content were compared among these groups. CsA was administered for the first 5 weeks to all groups. Results: The blood pressure was significantly higher in the high-sucrose LPD rats than in the NPD and the low-sucrose LPD rats. The supplement of Arg significantly decreased the blood pressure in the low-sucrose LPD rats. Urinary NOx, renal NO-generating capacity and the renal Arg content were significantly lower in the low-sucrose LPD rats than in the NPD rats. Arg supplementation to the LPD rats returned these values to the level of the NPD rats. Conclusion: The increase in blood pressure by LPD was associated with the higher amount of sucrose contained in LPD and the decrease in NO generation caused by the Arg depletion in rats with post-CsA nephropathy. For animal experiments we recommend that sucrose should not be used in LPD to balance the energy intake between LPD and NPD, and that a small amount of Arg be supplemented to LPD.